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When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given e.g. AUTHOR (year of submission) "Full thesis title", University of Southampton, name of the University School or Department, PhD Thesis, pagination http://eprints.soton.ac.uk UNIVERSITY OF SOUTHAMPTON FACULTY OF SCIENCE DEPARTMENT OF CHEMISTRY Doctor of Philosophy CHEMICAL AND ELECTROCHEMICAL NITRATIONS OF ALKENES AND DIENES by Andrew Jonathan Bloom ACKNOWLEDGEMENT I wish to thank the following: My parents for their support; Dr. John Mellor and Professor Martin Fleischmann, my supervisors; Dr. Philip Parsons for his faith and encouragement; Neil Smith, Ivan Pinto, Jeff Buchannan and Neil Carlson for the proof-reading and Suzanne Salt for the typing. Financial support from The Procurement Executive, Ministry of Defence, for my maintenance grant, and NATO, for travel expenses, is gratefully acknowledged. Table of Contents Chapter 1 Introduction 1 I'l Electrochemical Nitration 5 1-1,1 Anodic Oxidation of Dinitrogen Tetroxide 6 1*1,2 Anodic Oxidation of the Nitrite Ion 8 1-1,3 Anodic Oxidation of the Nitrate Ion 10 1-2 The Nitration of Alkenes and Dienes 12 1-2,1 The Reaction of Alkenes with Nitronium Salts 14 1-2,2 The Reaction of Acetyl Nitrate with Alkenes and Dienes 32 1-2,3 The Reaction of Dinitrogen Pentoxide with Alkenes and Dienes 46 1-2,4 The Reaction of Nitric Acid with Alkenes and Dienes 48 1-2,5 The Reaction of Tetranitromethane with Alkenes and Dienes 55 1-2,6 The Reaction of Nitryl Fluoride with Alkenes 60 1-2,7 The Reaction of Nitryl Chloride and Dinitrogen Tetroxide-Chlorine with Alkenes and Dienes 61 1-2,8 The Reaction of Nitryl Iodide and Dinitrogen Tetroxide with Alkenes and Dienes 63 1-2,9 The Reaction of Dinitrogen Tetroxide with Alkenes and Polyenes 65 1-2,10 The Reaction of Mercuric Nitrite with Alkenes 70 1-3 Initial Objectives 71 Chapter 2 The Electrogeneration of Nitronium Salts and Dinitrogen Pentoxide and Their Reactions 73 2-1 Introduction and Background 74 2"1,1 Mediated or Redox Catalysed Reactions 74 2-1,2 Electrochemically Generated Reagents 78 2-1,3 Chemical Preparation of Nitronium Salts and Dinitrogen Pentoxide 82 2-2 Results and Discussion i 84 2-2,1 Choice of Solvents 84 2-2,2 Choice of Electrolyte 85 2-2,3 Cell Design 86 2-2,4 Assay 88 2-2,5 Preparation and Reactions of Nitronium Tetrafluoroborate in Acetonitrile 89 2-2,6 Preparation and Reactions of Nitronium Hexafluorophosphate in Nitromethane 96 2-2,7 Generation of Nitronium Tetrafluoroborate in Sulpholane 101 2-2,8 Generation of Dinitrogen Pentoxide in Acetonitrile and Dichloromethane 101 2-3 Conclusions 109 Chapter 3 Nitroacetamidation of Alkenes and Dienes 110 3-1 Introduction and Background 111 3-1,1 Acetamidation Reactions: The Reaction of Electrophiles with Alkenes in Acetonitrile 111 3-1,2 Preparation of Vicinal Nitroamines 120 3-2 Results and Discussion 3-2,1 The Nitroacetamidation of Alkenes 124 3*2,2 The Nitroacetamidation of Dienes 140 3-2,3 Some Transformations of Nitroacetamides 152 3*3 Conclusions 157 Chapter 4 The Preparation of 1-Nitro-l,3-dienes Via the Nitrotrifluoroacetoxylation of Dienes 158 4*1 Introduction and Background 159 4*1,1 Reactions of Trifluoroacetyl Nitrate 159 4*1,2 Additions Involving the Trifluoroacetate Ion 160 4*1,3 Literature Preparations of 1-Nitro-l,3-Dienes 162 4*2 Results and Discussion 167 4*2,1 The Nitrotrifluoroacetoxylation of Dienes and the Preparation of 1-Nitro-l,3-dienes 167 4*2,2 The Nitrotrifluoroacetoxylation of Alkenes 174 4*2,3 Nucleophilic Additions to 1-Nitro-l,3-dienes 178 4*3 Conclusions 181 Chapter 5 Experimental Procedures 182 5*1 Materials 183 5*1,1 Purification of Solvents 183 5*1,2 Preparation and/or Purification of Electrolytes 183 5*1,3 Preparation and/or Purification of Starting Materials 183 5*1,4 Handling of Dinitrogen Tetroxide 184 5*1,5 Purification and Handling of Nitronium Tetrafluoroborate 184 5*1,6 Preparation and/or Purification of Other Reagents 185 5*1,7 Apparatus and Equipment 185 5*2 Electrochemistry Experiments 187 5*2,1 Typical Electrolysis Method 187 5-2,2 Analytical Method 187 5*2,3 Reactions of Electrogenerated Nitronium Tetrafluoroborate 189 5-2,4 Reactions of Electrogenerated Nitronium Hexafluorophosphate 191 5*2,5 Reaction of Electrogenerated Dinitrogen Pentoxide 193 5*3 The Nitroacetamidation of Alkenes 193 5*3,1 The Epimerisation of Nitroacetamides 202 5*3,2 The Reduction of Nitroacetamides 204 5*4 The Nitroacetamidation of Dienes 207 5*5 Oxidation and Reduction Reactions 215 5*6 Nitrotrifluoroacetoxylation: The Preparation of Nitrodienes 220 5*6,1 Typical Nitrotrifluoroacetoxylation Procedure 220 5*6,2 Typical Elimination Procedure 222 5*6,3 Nucleophilic Addition Reactions 227 References 230 UNIVERSITY OF SOUTHAMPTON ABSTRACT FACULTY OF SCIENCE CHEMISTRY Doctor of Philosophy CHEMICAL AND ELECTROCHEMICAL NITRATION OF ALKENES AND DIENES by Andrew Jonathan Bloom Anodic oxidation of dinitrogen tetroxide in acetonitrile containing lithium tetrafluoroborate gaue nitronium tetrafluoroborate in high yield and current efficiency. » Nitronium hexafluorophosphate in nitromethane and dinitrogen pentoxide in dichloromethane were similarly prepared. The electrogenerated nitration reagents were found to react with arenes, alkenes and/or silyenolethers giving the same products in similar yields to those obtained using the conventionally obtained reagents. Nitronium tetrafluoroborate in acetonitrile reacted with styrenes giving nitroacetamide products of Markounikou regiochemistry. trans-1-Phenylpropene and trans- stilbene underwent a syn addition, whilst cis-1-phenylpropene, cis-stilbene and 1-phenylcyclohexene all underwent an anti addition. The nitroacetamidation of simple alkenes gaue 1,2 and/or 1,3 adducts in low yield. Electrogenerated nitronium tetrafluoroborate in acetonitrile reacted with dienes to giue mixtures of 1,2 and 1,4 nitroacetamides. The additions onto isoprene and trans-penta-1,3-diene showed a preferential attack of the more substituted double bond. The 1,2 addition onto trans- penta-1,3-diene was syn whilst in both the 1,2 and 1,4 additions onto trans, trans hexa- 2,4-diene were non stereoselective. Oxidation of nitroacetamides with potassium permanganate or eerie aranonium nitrate under basic conditions gave acetamidoketones. Reduction of nitroacetamides with aluminium amalgam proceeded stereospecifically to give aminoacetamides. Heating the aminoacetamides caused cyclisation giving dihydroimidazoles. Mixtures of ammonium nitrate and trifluoroacetic anhydride reacted with dienes forming mixtures of nitrotrifluoroacetates. Treatment of these mixtures with a base such as potassium acetate gave 1-nitro-1,3-dienes, which were predominantly of the trans configuration. Attempted nitrotrifluoroacetoxylation of alkenes gave complex mixtures of products. The nucleophilic addition of thiophenol to trans-1-nitrobuta-1,3-diene gave mainly a 1,2 adduct, while the addition of aniline gave only a 1,4 adduct. Chapter One Introduction Nitration, the formation of a nitro-compound from an unsaturated compound, by reaction with a nitrating agent is a process of considerable popularity*. The process is commonly used to make aromatic nitro compounds, many of which are of industrial importance. Aromatic nitro compounds are used in the synthesis of explosives, 2 pharmaceuticals, dyes and fragrances, for example . (DH NO- O9N NO- HO3S SOoH NO- Trinitrotoluene Dinoserb an intermediate in an explosive a herbicide the synthesis of azo-dyes . Aliphatic nitro-compounds have considerably less industrial use. However they have become popular as 3 intermediates in research . This popularity is due to the diversity of useful reactions undergone by aliphatic nitro-compounds. R' -NH, R 'NO: NOz R-^R' NO; R' R OH Aliphatic nitro-compounds used in research are usually prepared by substitution: e.g. Nof e R^^NOo+Br or from other nitro-compounds: &g. R'Li R NO' or CdR2 R' Aromatic nitro-compounds are almost always prepared by nitration but the use of nitration of alkenes in the synthesis of aliphatic nitro-compounds is uncommon. There may be several reasons for this; many alkenes are unstable under the usual nitration conditions of concentrated 3 nitric acid or nitric acid-sulphuric acid mixtures: alkenes can undergo hydration, oxidation and polymerisation reactions in these media. Another reason is that many compounds available from nitration can be made in high yield from nitroalcohols. The nitroalcohols are prepared from condensation of a nitro-compound with an aldehyde. OCOCH OH R' R NO2 Many interesting nitration reactions, for example nitroacetamidation, are best carried out using nitronium salts which are expensive (for example N02BF^ El/g) or unpleasant to prepare and are extremely hydroscopic. The use of nitronium salts would be facilitated by an electrochemical preparation of the salts in a suitable solvent. Costs would be reduced by oxidising a cheap oxygenated-nitrogenous compound (eg. dinitrogen tetroxide, or a nitrate salt. The use of unpleasant reagents normally employed in the synthesis of nitronium salts (eg. anhydrous hydrogen fluoride, and fluorinated Lewis acids) would be avoided. The generation of the salts in the form of a solution would also allow reactions to be carried out using standard organic chemistry glassware and techniques. 4 I'l Electrochemical Nitration The standard procedure for the nitration of organic compounds involves concentrated nitric acid, either on its own or mixed with another acid.